With the discovery of a number of cancer-related genes in recent years, revelation of the mechanism of malignant transformation has been started gradually. As the results, it has been shown that many cancers are certain genetic diseases caused by the abnormality of genes. Since abnormal mutant cells are originated from normal cells by nature, they are not easily be recognized as foreign bodies in the living body and differences in their biological or biochemical properties are not so large unlike the case of infectious diseases caused by the invasion of other organisms.
In consequence, though various anticancer drugs, therapeutic methods and reagents have been developed, they exert influences upon not only cancer cells but also normal tissues and normal cells because of their low selectivity for cancer cells, so that, in the present situation, the use of such drugs is strictly restricted due to their side effects no matter how they are effective.
On the contrary, controlling methods of the expression of specific genes have recently been developed making use of nucleic acids and their derivatives. Since cancers are genetic diseases as described above, cancer cell-specific effects can fully be expected by such expression controlling methods when a specific gene, particularly a malignant transformation factor, is used as the target.
One of such means is antisense method. In this method, a short oligonucleotide (approximately 15 to 30 base length) having a nucleotide sequence complimentary to a nucleotide sequence of a gene to be used as a target is introduced into cells to effect inhibition of transcription or translation of the malignant transformation gene.
However, since single-stranded oligonucleotides to be used in the antisense method have low stability in cells and are quickly metabolized in the living body, they have not yet been realized as medicines.
On the other hand, expression of cell growth-related genes is naturally impelled in cancer cells due to their high cell division capacity. Because of this, these factors related to DNA synthesis and cell growth have been used as targets of anticancer agents. However, it is known that the degree of expression of each gene varies depending on each individual, organ and tissue type, and the degree varies greatly among cells even in the same cancer tissue. As the result, the conventional drugs in which a single cell growth factor is used as a target have limited efficacy due to narrow spectrum.
Accordingly, the object of the present invention is to provide an oligonucleotide or the derivative thereof useful as a pharmaceutical composition of an anticancer the like agent having broad spectrum and strong efficacy, as well as a method for preventing and treating cancers making use of the pharmaceutical composition.